Alpha2C-adrenoceptor modulators: a patent review

alpha2-Adrenoceptors are membrane proteins belonging to the superfamily of GPCRs. Detailed studies have shown three different subtypes, namely alpha2A, alpha2B and alpha2C. Although numerous alpha2-AR ligands exist, only a small set of compounds have shown even a degree of selectivity among the three alpha2-AR subtypes. Moreover, these compounds suffer from binding to receptor sites outside the alpha2-AR subfamily. Efforts made to understand the biological significance of each alpha2-AR subtype have greatly been assisted by genetically engineered mice. The main results obtained suggest that alpha2C-AR stimulation may represent a therapeutic strategy to get an analgesic response with reduced sedative effects and undesirable changes in blood pressure due to alpha2A-AR activation. This review summarizes the patent literature about the development of alpha2C-AR modulators from 2000 to early 2010 and their therapeutic effects evoked by the interaction with this receptor subtype. Over 90 patents have been deposited in the last 10 years regarding different methods of alpha2C-AR modulation (use of agonists or antagonists, nucleic acids and polypeptides) for diagnosis, prognosis and treatment of disorders involving this receptor. Nevertheless, despite the numerous published patents, ligands highly selective for the alpha2C-AR subtype, which continues to be enigmatic, are lacking.